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ALL-REZ BFM 2002: Multi-Center Study for Children With Relapsed Acute Lymphoblastic Leukemia

Primary Purpose

Lymphoblastic Leukemia, Acute, Lymphoma, Non-Hodgkin

Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
R-Blocks
Protocol II-Ida
Sponsored by
Charite University, Berlin, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoblastic Leukemia, Acute focused on measuring non-B ALL, relapse, treatment, Relapsed non-B ALL or non-B non-Hodgkin lymphoma

Eligibility Criteria

undefined - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Up to 18 years of age Morphologically confirmed diagnosis of relapsed non-B ALL or non-B non-Hodgkin lymphoma Exclusion Criteria: They have completed the 18th year of life at the time the relapse is diagnosed. Curative therapy is declined either by patient himself/herself or the respective legal guardian The patient is pregnant The patient is breast feeding Essential parts of the relapse therapy are declined either by the patient or his/her legal cannot be administered because of medical reasons. No consent is given for transmission of data The patient has a severe concomitant disease that does not allow treatment according to protocol (e.g. malformation syndromes, cardiac malformations, metabolic disorders).

Sites / Locations

  • ALL-REZ Studienzentrale

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

R-Blöcke

Prot-II-Ida

Arm Description

Blocktherapie

a

Outcomes

Primary Outcome Measures

Reduction of MRD
event-free and overall survival
the toxicity associated with each treatment strategy

Secondary Outcome Measures

Improvement of the prognosis in the intermediate risk group using the stratification in treatment arms with and without allogenic SCT based on the MRD result after the second treatment element of induction therapy

Full Information

First Posted
June 14, 2005
Last Updated
February 1, 2013
Sponsor
Charite University, Berlin, Germany
Collaborators
Deutsche Kinderkrebsstiftung
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1. Study Identification

Unique Protocol Identification Number
NCT00114348
Brief Title
ALL-REZ BFM 2002: Multi-Center Study for Children With Relapsed Acute Lymphoblastic Leukemia
Official Title
ALL-REZ BFM 2002: Protocol for the Treatment of Children With Relapsed Acute Lymphoblastic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
August 2003 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Charite University, Berlin, Germany
Collaborators
Deutsche Kinderkrebsstiftung

4. Oversight

5. Study Description

Brief Summary
The protocol ALL-REZ BFM 2002 aims at the optimization of treatment for children with relapsed acute lymphoblastic leukemia. The primary objective of study ALL-REZ BFM 2002 is the randomized comparison of a lower dosed and less intensive, but continuous consolidation therapy with conventional therapy administered in treatment blocks. Outcome measures are the reduction of minimal residual disease (MRD), event-free and overall survival, and the toxicity associated with each treatment strategy.
Detailed Description
The study is based on the results of five consecutive trials performed by the ALL-REZ BFM study group since 1983. Thus the study meets the criteria of evidence-based therapy, which has been developed over nearly 20 years. Multi-agent chemotherapy in short intensive courses, which are separated by treatment-free intervals, has proved to be a successful form of induction and consolidation therapy. It is followed by preventative (or therapeutic) cranial irradiation and continuation therapy. A number of risk factors, particularly the time of relapse, site of relapse, and the ALL immunophenotype, allow the stratification of patients into a group that has an acceptable prognosis after treatment with chemotherapy alone and a second group that has a high risk of subsequent recurrence following the achievement of a second remission. The latter group requires further intensification of consolidation therapy by allogenic stem cell transplantation (SCT). To date, the indication for SCT has remained unclear for a large and heterogeneous group of patients with an intermediate prognosis. During the precursor study ALL-REZ BFM 96, however, the amount of minimal residual disease (MRD) determined quantitatively with clonal molecular markers after the second induction therapy element was shown to be a highly significant predictor of relapse-free survival. The primary objective of study ALL-REZ BFM 2002 is the randomized comparison of a lower dosed and less intensive, but continuous consolidation therapy with conventional therapy administered in treatment blocks. Outcome measures are the reduction of MRD, event-free and overall survival, and the toxicity associated with each treatment strategy. The secondary objectives include an improvement of the prognosis in the intermediate risk group using the stratification in treatment arms with and without allogenic SCT based on the MRD result after the second treatment element of induction therapy. An additional aim is to improve the remission induction rate in all groups by increasing the treatment intensity during induction. This is achieved by shortening the intervals between treatment blocks in keeping with the principles of guiding therapy as defined in the protocol. A series of biological companion studies aims to advance our understanding of the disorder and to establish novel prognostic factors that will allow a risk-adapted therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoblastic Leukemia, Acute, Lymphoma, Non-Hodgkin
Keywords
non-B ALL, relapse, treatment, Relapsed non-B ALL or non-B non-Hodgkin lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
338 (Actual)

8. Arms, Groups, and Interventions

Arm Title
R-Blöcke
Arm Type
Active Comparator
Arm Description
Blocktherapie
Arm Title
Prot-II-Ida
Arm Type
Experimental
Arm Description
a
Intervention Type
Procedure
Intervention Name(s)
R-Blocks
Intervention Type
Procedure
Intervention Name(s)
Protocol II-Ida
Primary Outcome Measure Information:
Title
Reduction of MRD
Time Frame
a
Title
event-free and overall survival
Time Frame
a
Title
the toxicity associated with each treatment strategy
Time Frame
a
Secondary Outcome Measure Information:
Title
Improvement of the prognosis in the intermediate risk group using the stratification in treatment arms with and without allogenic SCT based on the MRD result after the second treatment element of induction therapy
Time Frame
a

10. Eligibility

Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Up to 18 years of age Morphologically confirmed diagnosis of relapsed non-B ALL or non-B non-Hodgkin lymphoma Exclusion Criteria: They have completed the 18th year of life at the time the relapse is diagnosed. Curative therapy is declined either by patient himself/herself or the respective legal guardian The patient is pregnant The patient is breast feeding Essential parts of the relapse therapy are declined either by the patient or his/her legal cannot be administered because of medical reasons. No consent is given for transmission of data The patient has a severe concomitant disease that does not allow treatment according to protocol (e.g. malformation syndromes, cardiac malformations, metabolic disorders).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Günter Henze, Prof.Dr.med.
Organizational Affiliation
German Society for Pediatric Oncology and Hematology GPOH gGmbH
Official's Role
Principal Investigator
Facility Information:
Facility Name
ALL-REZ Studienzentrale
City
Berlin
ZIP/Postal Code
13353
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
15158091
Citation
Taube T, Eckert C, Korner G, Henze G, Seeger K. Real-time quantification of TEL-AML1 fusion transcripts for MRD detection in relapsed childhood acute lymphoblastic leukaemia. Comparison with antigen receptor-based MRD quantification methods. Leuk Res. 2004 Jul;28(7):699-706. doi: 10.1016/j.leukres.2003.11.006.
Results Reference
result
PubMed Identifier
15257960
Citation
Eckert C, Einsiedel HG, Hartmann R, von Stackelberg A, Volpel S, Guggemos A, Hanzsch N, Kawan L, Seeger K, Henze G. Clonal stability of initial leukemia in a child with central nervous system relapse 7.4 years after bone marrow relapse of common acute lymphoblastic leukemic. Haematologica. 2004 Jul;89(7):ECR23.
Results Reference
result
PubMed Identifier
15014526
Citation
Wellmann S, Guschmann M, Griethe W, Eckert C, von Stackelberg A, Lottaz C, Moderegger E, Einsiedel HG, Eckardt KU, Henze G, Seeger K. Activation of the HIF pathway in childhood ALL, prognostic implications of VEGF. Leukemia. 2004 May;18(5):926-33. doi: 10.1038/sj.leu.2403332. Erratum In: Leukemia. 2004 Jun;18(6):1164. Stackelberg Av [corrected to von Stackelberg A].
Results Reference
result
PubMed Identifier
14752084
Citation
Herold R, von Stackelberg A, Hartmann R, Eisenreich B, Henze G. Acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Munster Group (ALL-REZ BFM) experience: early treatment intensity makes the difference. J Clin Oncol. 2004 Feb 1;22(3):569-70; author reply 570-1. doi: 10.1200/JCO.2004.99.153. No abstract available.
Results Reference
result
PubMed Identifier
34010787
Citation
Eckert C, Parker C, Moorman AV, Irving JA, Kirschner-Schwabe R, Groeneveld-Krentz S, Revesz T, Hoogerbrugge P, Hancock J, Sutton R, Henze G, Chen-Santel C, Attarbaschi A, Bourquin JP, Sramkova L, Zimmermann M, Krishnan S, von Stackelberg A, Saha V. Risk factors and outcomes in children with high-risk B-cell precursor and T-cell relapsed acute lymphoblastic leukaemia: combined analysis of ALLR3 and ALL-REZ BFM 2002 clinical trials. Eur J Cancer. 2021 Jul;151:175-189. doi: 10.1016/j.ejca.2021.03.034. Epub 2021 May 16.
Results Reference
derived
PubMed Identifier
31644328
Citation
Eckert C, Groeneveld-Krentz S, Kirschner-Schwabe R, Hagedorn N, Chen-Santel C, Bader P, Borkhardt A, Cario G, Escherich G, Panzer-Grumayer R, Astrahantseff K, Eggert A, Sramkova L, Attarbaschi A, Bourquin JP, Peters C, Henze G, von Stackelberg A; ALL-REZ BFM Trial Group. Improving Stratification for Children With Late Bone Marrow B-Cell Acute Lymphoblastic Leukemia Relapses With Refined Response Classification and Integration of Genetics. J Clin Oncol. 2019 Dec 20;37(36):3493-3506. doi: 10.1200/JCO.19.01694. Epub 2019 Oct 23.
Results Reference
derived
PubMed Identifier
26001791
Citation
Karawajew L, Dworzak M, Ratei R, Rhein P, Gaipa G, Buldini B, Basso G, Hrusak O, Ludwig WD, Henze G, Seeger K, von Stackelberg A, Mejstrikova E, Eckert C. Minimal residual disease analysis by eight-color flow cytometry in relapsed childhood acute lymphoblastic leukemia. Haematologica. 2015 Jul;100(7):935-44. doi: 10.3324/haematol.2014.116707. Epub 2015 May 22.
Results Reference
derived
PubMed Identifier
25253770
Citation
Irving J, Matheson E, Minto L, Blair H, Case M, Halsey C, Swidenbank I, Ponthan F, Kirschner-Schwabe R, Groeneveld-Krentz S, Hof J, Allan J, Harrison C, Vormoor J, von Stackelberg A, Eckert C. Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition. Blood. 2014 Nov 27;124(23):3420-30. doi: 10.1182/blood-2014-04-531871. Epub 2014 Sep 24.
Results Reference
derived
PubMed Identifier
23775972
Citation
Eckert C, Henze G, Seeger K, Hagedorn N, Mann G, Panzer-Grumayer R, Peters C, Klingebiel T, Borkhardt A, Schrappe M, Schrauder A, Escherich G, Sramkova L, Niggli F, Hitzler J, von Stackelberg A. Use of allogeneic hematopoietic stem-cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate-risk group. J Clin Oncol. 2013 Jul 20;31(21):2736-42. doi: 10.1200/JCO.2012.48.5680. Epub 2013 Jun 17.
Results Reference
derived
PubMed Identifier
21940824
Citation
Willer A, Gerss J, Konig T, Franke D, Kuhnel HJ, Henze G, von Stackelberg A, Moricke A, Schrappe M, Boos J, Lanvers-Kaminsky C. Anti-Escherichia coli asparaginase antibody levels determine the activity of second-line treatment with pegylated E coli asparaginase: a retrospective analysis within the ALL-BFM trials. Blood. 2011 Nov 24;118(22):5774-82. doi: 10.1182/blood-2011-07-367904. Epub 2011 Sep 22.
Results Reference
derived
PubMed Identifier
21828124
Citation
Shalapour S, Hof J, Kirschner-Schwabe R, Bastian L, Eckert C, Prada J, Henze G, von Stackelberg A, Seeger K. High VLA-4 expression is associated with adverse outcome and distinct gene expression changes in childhood B-cell precursor acute lymphoblastic leukemia at first relapse. Haematologica. 2011 Nov;96(11):1627-35. doi: 10.3324/haematol.2011.047993. Epub 2011 Aug 9.
Results Reference
derived
Links:
URL
http://www.kinderkrebsinfo.de/
Description
ALL-REZ BFM 2002

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ALL-REZ BFM 2002: Multi-Center Study for Children With Relapsed Acute Lymphoblastic Leukemia

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